Depolarization of the external membrane of cardiac and skeletal muscle results in release of Ca2+ from intracellular stores, which in turn, elicits contraction. The voltage sensor of the external membrane is the dihydropyridine receptor (DHPR) and the protein responsible for Ca2+ release is the Ca2+ release channel of sarcoplasmic reticulum, also know as the ryanodine receptor (RyR). The mechanism by which DHPRs open RyR and elicit contraction is unknown, but recent findings suggest that a specific segment of the DHPR may be directly connected to RyR. Imperatoxin A (IpTxa), a 33 amino acid scorpion toxin that opens RyR with high affinity, may provide information regarding the exact amino acids involved in the interaction between DHPR and RyR and the nature of the reaction involved. The binding of IpTxa is displaced by a 22 amino acid segment of the DHPR and both, IpTxa and the DHPR segment loose their capacity to open RyR when a Thr (in IpTxa) or Ser (in DHPR) is replaced by a negatively-charged amino acid. Thus, IpTxa open Ryr in a manner which is similar to the natural DHPR-RyR interaction. Elucidation of the three-dimensional structure of IpTxa will add significantly to our understanding of how DHPR interacts with RyR.